Anti-beta-glucan-like immunoprotective candidacidal antiidiotypic antibodies

Abstract

Mycoses, candidiasis in particular, are relatively common opportunistic infections still characterized by an unacceptable high mortality rate. Furthermore, they are often complicated by resistance or refractoriness to the existing antimicrobial agents. In recent years new effective therapeutic and large-scale preventative strategies have been proposed by exploiting the identification of fungal beta-glucans as target of antifungal agents such as echinocandins, yeast killer toxins and protective antibodies. Anti-beta-glucan antibodies are detectable in animal and human sera. When elicited by glucan-based vaccines they can exert a fungicidal protective activity. Beta-glucan cell wall killer toxin receptors can elicit fungicidal protective antibodies following natural and experimental infections. When used as an immunogen a killer toxin-neutralizing monoclonal antibody (beta-glucan-like) is able to elicit a significant anticandidal protection mediated by anti-idiotypic anti-beta-glucan-like candidacidal antibodies. Polyclonal, monoclonal and recombinant anti-beta-glucan-like antibodies and peptide mimotopes are able to exert an in vitro and/or in vivo microbicidal activity against eukaryotic and prokaryotic killer toxin receptor-bearing pathogenic microorganisms. Implications and perspectives for transphyletic anti-infectious control strategies, as immunoprevention and immunotherapy, are discussed.

Yeast Killer Toxin-Like Candidacidal Ab6 Antibodies Elicited through the Manipulation of the Idiotypic Cascade

“…In this sense, these latter interactions (KT-KTR) could be similar to those between selected Ab5-like peptides and elicited Ab6, suggesting that these peptides represent functional KTR immunogenic mimics, as they stimulate the production of candidacidal Abs. Since KTR seems to consist of β-1,3-glucans [18], this study confirm the potential of peptides, as those selected from phage display libraries, to mimic carbohydrate Ags, although the molecular mechanisms that enable such mimicking remain to be elucidated.…”

“…MAb K10 was produced by immunization of animals with a KT-neutralizing mAb (mAb KT4, Ab1) which proved to have functional relatedness to KTR [15]–[19]. MAb K10 competed with KT for binding to specific KTR, distributed mainly in budding cells and germination tubes, which consist essentially of β-1,3-glucans [16], [18], [19]. MAb KT4 was able indeed to neutralize the candidacidal activity of mAb K10 against KT-sensitive C. albicans cells [14].…”

Vaccine and Monoclonal Antibody That Enhance Mouse Resistance to Candidiasis

“…We asked whether the anti-Fba antibodies could exert a direct anti-Candida effect. We tested the in vitro candidacidal activity of MAb E2-9 by following the method described by Magliani et al (38). In preliminary investigations in which we tested only several concentrations of antibody and fungal cells, the differences in the candidacidal assays between the tested MAb E2-9 groups and controls were not significant.…”

A Wickerhamomyces anomalus Killer Strain in the Malaria Vector Anopheles stephensi

“…The mechanism of action of Wa KTs is mainly based on the interaction with cell-wall carbohydrates, where β-glucanase-induced hydrolysis of glucan into glucose is demonstrated [18]. In this context, several authors have investigated the β-glucanase activity of Wa KTs from different W. anomalus strains.…”